The general aim of this project is study the effects of immunotoxin induced transient T-cell depletion on the erasure of T-cell memory, and to use this knowledge for the experimental and clinical treatment of T cell driven autoimmune diseases, graft-versus-host disease, AIDS and the induction of tolerance to organ transplants. 1-2-3 day course of anti-rhesus CD3 immunotoxin constructed with CRM9, a binding site mutant of diphtheria toxin, depletes lymph node and blood T cells by 98% without systemic toxicity. This process is associated with a marked prolongation of survival of mismatched functioning kidney transplants. When donor bone marrow cells are also given intravenously or donor lymphoid tissue by thymic injection, long term tolerance to the grafts is achieved without the use of immunosuppressive drugs. Experimental allergic encephalomyelitis (EAE) is moderated in rhesus monkeys by anti-CD3 immunotoxin. Peripheral T cell effector functions are largely eliminated in the periphery but only moderated with the CNS, probably due to the role of the blood brain barrier.